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Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する). 信州大学, 2020, 博士論文.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601甲第1198号"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000516579800007"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "31754214"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/31754214/", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1038/s41388-019-1112-z"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1038/s41388-019-1112-z", "subitem_relation_type_select": "DOI"}}]}, "item_14_select_71": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "学位の区分", "attribute_value_mlt": [{"subitem_text_value": "doctoral"}]}, "item_14_text_12": {"attribute_name": "学位の分野", "attribute_value_mlt": [{"subitem_text_value": "医学"}]}, "item_14_text_13": {"attribute_name": "学位の報告番号", "attribute_value_mlt": [{"subitem_text_value": "甲第1198号"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "EPITHELIAL-MESENCHYMAL TRANSITION; SQUAMOUS-CELL CARCINOMAS; PANCREATIC-CANCER; POOR-PROGNOSIS; VASCULAR INTEGRITY; BREAST-CANCER; UP-REGULATION; PODOPLANIN; EXPRESSION; INVASION"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Tumor metastasis is a primary source of morbidity and mortality in cancer. Adrenomedullin (AM) is a multifunctional peptide regulated by receptor activity-modifying proteins (RAMPs). We previously reported that the AM-RAMP2 system is involved in tumor angiogenesis, but the function of the AM-RAMP3 system remains largely unknown. Here, we investigated the actions of the AM-RAMP2 and 3 systems in the tumor microenvironment and their impact on metastasis. PAN02 pancreatic cancer cells were injected into the spleens of mice, leading to spontaneous liver metastasis. Tumor metastasis was enhanced in vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-). By contrast, metastasis was suppressed in RAMP3-/- mice, where the number of podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) was reduced in the periphery of tumors at metastatic sites. Because PDPN-positive CAFs are a hallmark of tumor malignancy, we assessed the regulation of PDPN and found that Src/Cas/PDPN signaling is mediated by RAMP3. In fact, RAMP3 deficiency CAFs suppressed migration, proliferation, and metastasis in co-cultures with tumor cells in vitro and in vivo. Moreover, the activation of RAMP2 in RAMP3-/- mice suppressed both tumor growth and metastasis. Based on these results, we suggest that the upregulation of PDPN in DI-E-RAMP2-/- mice increases malignancy, while the downregulation of PDPN in RAMP3-/- mice reduces it. Selective activation of RAMP2 and inhibition of RAMP3 would therefore be expected to suppress tumor metastasis. This study provides the first evidence that understanding and targeting to AM-RAMP systems could contribute to the development of novel therapeutics against metastasis."}]}, "item_1627890986942": {"attribute_name": "出版タイプ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_be7fb7dd8ff6fe43", "subitem_version_type": "NA"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "open access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_abf2"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "戴, 昆", "creatorNameLang": "ja"}], "nameIdentifiers": [{"nameIdentifier": "109535", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "16MH203A_yoshi.pdf", "filesize": [{"value": "130.7 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 130699.99999999999, "url": {"label": "内容の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21408/files/16MH203A_yoshi.pdf"}, "version_id": "850a1031-55ff-4bc4-b7e6-f4492b05e869"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 1, "filename": "16MH203A_shinsa.pdf", "filesize": [{"value": "95.3 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 95300.0, "url": {"label": "審査結果の要旨", "url": "https://soar-ir.repo.nii.ac.jp/record/21408/files/16MH203A_shinsa.pdf"}, "version_id": "e403aa32-d1c1-4d0d-b2dc-0de7c7e8e30a"}, {"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2020-06-12"}], "displaytype": "detail", "download_preview_message": "", "file_order": 2, "filename": "16MH203A_ronbun.pdf", "filesize": [{"value": "2.2 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_note", "mimetype": "application/pdf", "size": 2200000.0, "url": {"label": "博士論文の全文", "objectType": "fulltext", "url": "https://soar-ir.repo.nii.ac.jp/record/21408/files/16MH203A_ronbun.pdf"}, "version_id": "4ce1066b-9612-4fe2-893d-75666c927aa5"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "doctoral thesis", "resourceuri": "http://purl.org/coar/resource_type/c_db06"}]}, "item_title": "Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する)", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する)", "subitem_title_language": "en"}]}, "item_type_id": "14", "owner": "1", "path": ["849"], "permalink_uri": "http://hdl.handle.net/10091/00022165", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2020-06-15"}, "publish_date": "2020-06-15", "publish_status": "0", "recid": "21408", "relation": {}, "relation_version_is_last": true, "title": ["Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する)"], "weko_shared_id": -1}
Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する)
http://hdl.handle.net/10091/00022165
http://hdl.handle.net/10091/000221657840dafd-0da4-4185-86f6-b39e9dd6c039
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内容の要旨 (130.7 kB)
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審査結果の要旨 (95.3 kB)
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博士論文の全文 (2.2 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-06-15 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
戴, 昆
× 戴, 昆 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 戴 昆. Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through modification of cancer-associated fibroblasts (アドレノメデュリン(AM)-RAMP3系の欠損は、癌関連線維芽細胞の性質を変化させ、臓器間転移を抑制する). 信州大学, 2020, 博士論文. | |||||
書誌情報 |
発行日 2020-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1198号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2020-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13601 | |||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1198号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。ONCOGENE. 39(9):1914-1930 (2020); doi:10.1038/s41388-019-1112-z. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://pubmed.ncbi.nlm.nih.gov/31754214/ | |||||
関連名称 | 31754214 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41388-019-1112-z | |||||
関連名称 | 10.1038/s41388-019-1112-z | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000516579800007 |